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Biomedical subjects

C Johnston

Publications and source records attributed to C Johnston.

At least 37 records · Page 2Linked to original sources
PubMed2004

Kinematic evaluation of the back in fully functioning riding horses.

REASONS FOR PERFORMING STUDY: Clinical history and examination are important features in diagnosis of equine back dysfunction. However, interpretation is subjective and therefore may vary substantially. OBJECTIVES: To establish a clinical tool to objectively evaluate the function of the equine back, in the form of a database on the kinematics of the back at the walk and trot in fully functioning riding horses. METHODS: Thirty-three fully functioning riding horses walked and trotted on a treadmill. Morphometrics and kinematics were tested for correlations to age, height, weight and stride length, and differences between gender (geldings and mares) and use (dressage and showjumping). RESULTS: A database for range of movement and symmetry of movement for extension and flexion, lateral bending, lateral excursion and axial rotation was presented. Symmetry values were very high for all variables. Significant differences were observed in use and gender. Age was negatively correlated to extension and flexion of the thoracolumbar junction. CONCLUSIONS: Interrelationships between use, gender and age to conformation and movement were established. POTENTIAL RELEVANCE: The database provides a basis for objective reference for diagnosis, therapy and rehabilitation of clinical cases of back dysfunction.

Age Factors↗
PubMed2003

Surgeon workload and survival from breast cancer.

The formation of multidisciplinary breast teams across the UK is intended to concentrate the assessment and treatment of breast cancer into the hands of high volume specialists. We undertook a retrospective population-based study in order to determine the trends in surgeon breast cancer workload in Yorkshire, UK, and to investigate whether patients treated by low-workload surgeons had poorer survival. Of 11 329 female breast cancer patients diagnosed in 1989-1994 in Yorkshire, 6% were managed by surgeons with a mean annual workload of less than 10 new patients, while surgeons with workloads of 10-29, 30-49 and >50 treated 21, 21 and 52%, respectively. Over the study period, increasing number of patients were managed by surgeons with higher workloads. Patients treated by low-workload surgeons had poorer survival. Five-year survival was 60% in the lowest workload category compared to 68% in the highest category. The relative risk of death was increased by 15% (RR=1.15, 95% CI 1.03-1.28) and by 10% (RR=1.10, 95% CI 1.02-1.18) for patients managed by surgeons with workloads <10 and 10-29 cases per annum in comparison to patients managed by surgeons with workloads of >50. The results of this study suggest increasing site specialisation in breast cancer among general surgeons. It also provides further evidence that the management of patients by surgeons with low workloads decreases overall survival.

Adult↗
PubMed2003

Feasibility and compliance of automated measurement of quality of life in oncology practice.

PURPOSE: Systematic quality-of-life (QOL) assessment may have value in oncology practice by increasing awareness of a wide range of issues, possibly increasing detection of psychologic morbidity, social problems, and changes in physical status, and improving care and its outcomes. However, logistic problems are substantial. Automated systems solve many of these problems. We field-tested the feasibility and compliance that can be achieved using a computer touchscreen system in two consecutive studies. PATIENTS AND METHODS: In study 1, a prospective cohort of 272 patients was offered QOL assessment at each clinic appointment for 6 months. In study 2, all patients (N = 1,291) were offered QOL assessment as part of clinic routine during a 12-week period. RESULTS: In study 1, 82% of patients agreed to take part, but over time, compliance was poor (median, 40%; mean, 43%) and deteriorated with longer follow-up. In study 2, the overall compliance was greatly increased (median, 100%; mean, 70%), and compliance was retained over multiple visits. In study 1, compliance was better in younger patients, males, and socially advantaged patients, but was not affected by the presence of depression or anxiety, or QOL. In the second study, building on experience in the first study, data collection and storage in the computer system was excellent, achieving 98% of collected data stored in one center. In general, patients were comfortable with the computers and the approach. Data collection on the wards was more difficult and less complete than in clinics, especially for patients undergoing acute admissions. CONCLUSION: Feasibility with higher compliance was demonstrated in study 2, in which the data collection was integrated into routine care, and can be improved with further technical initiatives and education of staff.

Adult↗
PubMed2003

An integrative physiological approach to polyuria and hyponatraemia: a 'double-take' on the diagnosis and therapy in a patient with schizophrenia.

A patient with a history of schizophrenia was brought to the emergency department with extensive self-inflicted soft tissue injuries. Primary polydipsia was evident on admission, because he had a maximally dilute urine, a urine flow rate of 10 ml/min, and hyponatraemia (100 mmol/l). During an imaginary consultation with Professor McCance in which he applied basic principles of integrative physiology and a deductive analysis in quantitative terms, other reasons for the polyuric state were considered. Moreover, based on the very low value for the concentration of urea in plasma (< 0.7 mmol/l, BUN 1 mg /dl), the goals of therapy to prevent osmotic demyelination became evident. Applying this simple approach, a more comprehensive and accurate differential diagnosis, and a plan for therapy to avoid serious complications was compiled.

Adult↗
PubMed2003

How complete has skin cancer registration been in the UK? A study from Yorkshire.

The completeness of skin cancer registration in the Yorkshire region was evaluated for the year 1994 by the independent case ascertainment method. Patients diagnosed with skin cancer were identified from regional pathology laboratories, inpatient and outpatient hospital departments and general practices, and were matched against records held by the Northern and Yorkshire Cancer Registry and Information Services (NYCRIS). Out of 5987 skin cancer cases identified from 14 pathology laboratories, 123 general practices, 16 NHS Trusts inpatient databases and 7 dermatology outpatient departments, 83.5% had a matching record on the Cancer Register. The proportion of registered malignant melanoma (MM) and non-melanoma skin cancer (NMSC) cases were 87.5% (95% confidence interval (CI) 84.0-90.4) and 83.1% (95% CI 81.9-84.2) respectively. Skin cancers found in the pathology laboratories, the main notification sources of the registry, were under-ascertained by 15% (10% MM and 15% NMSC). Cases identified from general practices had a significantly lower proportion of matching registry records in comparison with other information sources. No record of histological confirmation could be found for 11% MM and 13% NMSC. Complete capture of pathology laboratory information, histological confirmation of all lesions suspected of skin cancer and routine receipt of hospital patient administration system information supplementary to that from pathology laboratories are measures that would provide the most substantial improvement to ascertainment of skin cancer data.

Ambulatory Care Facilities↗
PubMed2002

Comparison of survival, palliation, and quality of life with three chemotherapy regimens in metastatic colorectal cancer: a multicentre randomised trial.

BACKGROUND: This randomised trial compared three chemotherapy regimens in the first-line treatment of advanced colorectal cancer, in terms of their effect on overall and progression-free survival; other endpoints included toxicity, symptom palliation, and quality of life. METHODS: 905 patients were randomly assigned the de Gramont regimen (n=303; folinic acid 200 mg/m(2), fluorouracil bolus 400 mg/m(2), and infusion 600 mg/m(2) on days 1 and 2, repeated every 14 days), the Lokich regimen (n=301; protracted venous infusion of fluorouracil 300 mg/m(2) daily), or raltitrexed (n=301; 3 mg/m(2) intravenously every 21 days). Analyses were by intention to treat. FINDINGS: Median follow-up of survivors was 67 weeks. For the de Gramont, Lokich, and raltitrexed groups, respectively, median survival was 294, 302, and 266 days. The hazard ratios for overall survival were 0.88 (95% CI 0.70-1.12, p=0.17) for de Gramont versus Lokich, and 0.99 (0.79-1.25, p=0.94) for de Gramont versus raltitrexed. An increase in treatment-related deaths was seen on raltitrexed (de Gramont one, Lokich two, raltitrexed 18) due to combined gastrointestinal and haematological toxicity. Patients' assessment of quality of life showed that raltitrexed was inferior to the fluorouracil-based regimens, especially in terms of palliation and functioning. INTERPRETATION: The deGramont and Lokich regimens were similar in terms of survival, quality of life, and response rates. The Lokich regimen was associated with more central line complications and hand-foot syndrome. Raltitrexed showed similar response rates and overall survival to the de Gramont regimen and was easier to administer, but resulted in greater toxicity and inferior quality of life.

Adenocarcinoma↗
PubMed2002

Comparison of the RNA-amplification based methods RT-PCR and NASBA for the detection of circulating tumour cells.

Increasingly, reverse transcriptase polymerase chain reaction (RT-PCR) is used to detect clinically significant tumour cells in blood or bone marrow. This may result in a redefinition of disease-free and clinical relapse. However, its clinical utility may be limited by lack of automation or reproducibility. Recent studies have suggested nucleic acid sequence-based amplification of target RNA may be more robust. In this study, nucleic acid sequence-based amplification was established to detect melanoma, colorectal and prostate cancer cells. Nucleic acid sequence-based amplification and RT-PCR both successfully amplified target RNA in peripheral blood samples from patients with melanoma and colorectal cancer, but only RT-PCR detected PSA in blood samples from patients with prostate cancer. There was relatively good agreement between sample replicates analyzed by RT-PCR (Kappa values of one for tyrosinase, 0.67 for CK-20 and one for PSA), but less agreement when analyzed by nucleic acid sequence-based amplification. This may limit the routine use of NASBA for the detection of clinically significant disease. In summary, RT-PCR appears at present to be the most reliable and reproducible method for the detection of low-level disease in cancer patients, although prospective studies are warranted to assess the clinical utility of different molecular diagnostic methods.

Colorectal Neoplasms↗
PubMed2002

Does smoking increase relapse rates in Graves' disease?

We wondered whether the relapse rate of Graves' hyperthyroidism was increased amongst patients who smoked. To this end, a retrospective analysis of clinical and laboratory data of consecutive patients with Graves' disease was carried out. All patients were treated with thionamide anti-thyroid drugs (ATD) for at least one year and remission was defined as continued and biochemical euthyroidism, at least 6 months after discontinuing ATD. The study comprised 221 subjects with Graves' disease from a hospital-based population over 9 years. We took the following variables into account when assessing contribution to disease relapse: Goiter, Thyroid Associated Ophthalmopathy (TAO), and Time to euthyroidism after starting ATD and interaction between smoking and sex. Smoking had a marginally significant (p=0.081) deleterious effect on the likelihood of remission after ATD treatment for Graves' disease. The effect of smoking was, however, highly significant in males and indeed the deleterious effect on remissions may be restricted to males (odds ratio, 11.1; 95% confidence interval, 1.25 to 98.5). The presence of goiter (odds ratio, 3.8; 95% confidence interval, 2.05 to 7.1) and TAO (odds ratio, 1.8; 95% confidence interval, 0.993 to 3.18) forecasted lower chances of achieving remission. The shorter the time a patient became euthyroid after starting ATD the more likely his disease was to remit. We conclude that cigarette smoking increases the likelihood of Graves' disease recurrence in males treated with anti-thyroid drugs. Thus, smoking appears to be an important risk factor in the pathogenesis and outcome of Graves' disease patients at least in subsets of patients.

Adult↗
PubMed2002

Long-term implantation of preadipocyte-seeded PLGA scaffolds.

Studies were performed in a long-term effort to develop clinically translatable, tissue engineered adipose constructs for reconstructive, correctional, and cosmetic indications. Rat preadipocytes were harvested, isolated, expanded ex vivo, and seeded within PLGA scaffolds. Preadipocyte-seeded and acellular (control) scaffolds were implanted for 1-12 months. Explanted scaffolds were stained with osmium tetroxide, processed, and counterstained using H&E. Quantitative histomorphometric analysis was performed on all tissue sections to determine the amount of adipose tissue formed. Analyses revealed maximum adipose formation at 2 months, followed by a decrease at 3 months, and complete absence of adipose and PLGA at 5-12 months. These results extend a previous short-term study (Tissue Engineering 1999;5:134) and demonstrate that adipose tissue can be formed in vivo using tissue engineering strategies. However, the long-term maintenance of adipose tissue remains elusive.

Adipocytes↗
PubMed2002

Effect of conformational aspects on the movement of the equine back.

The relationship between structure and function is important in the judgement of the horse. Twenty sound riding horses walked and trotted on a treadmill. The movement of the backs of each of the horses was measured using a commercially available movement analysis system. Morphometric, spatiotemporal and kinematic information were correlated to investigate the effect of conformation on movement. Taller and heavier horses seem to have longer thoracic and lumbar backs, and are wider at the pelvis. Horses with longer strides extended and flexed their backs in the caudal saddle region to a greater extent at the walk, but not the trot. Horses with greater angle of L5 tend to extend and flex this region of the back more. At the walk and trot, a long thoracic back results in greater lumbar lateral bending. A negative relationship was found between the curvature of mid-thoracic back and the amount of lateral bending of L1 and L3 and axial rotation of the pelvis at the trot. There are clear relationships between back conformation and movement that may be important to the orthopaedic health of the horse. Further understanding of the relationships between conformation, movement and injury may provide an objective basis for the evaluation of future performance and soundness.

Animals↗
PubMed2002

Influence of draw reins on ground reaction forces at the trot.

According to riding texts, draw reins are supposed to support increased collection. This has not been measured objectively. Therefore, the objective of this study was to determine whether a horse ridden with draw reins would relatively increase weightbearing of the hindquarters while worked with the draw reins compared to a normal rein. Ground reaction forces were measured in 8 horses at the slow trot over a force plate in 3 different experimental set-ups: 1) riding with only a draw rein (DR); 2) riding with the combination of a normal and a draw rein (NR-DR) and 3) riding with a normal rein (NR). Horses ridden with NR-DR showed significant higher vertical impulse in the hindlimb compared to riding both with only DR and only NR. Several significant differences were also seen in the horizontal force. It is concluded that draw reins, when used correctly, together with a normal rein, achieve the desired result of shifting the weight of the horse caudally. This was not the case when the draw rein was used alone. It is important that trainers, as well as veterinarians, recommending draw reins in a rehabilitation programme, know about these possible effects.

Animal Husbandry↗
PubMed2002

Repeatability of back kinematics in horses during treadmill locomotion.

We tested the hypothesis that repeatability of a standardised protocol for quantifying back kinematics is sufficiently high not to prevent its use in the clinical evaluation of horses with back problems. We investigated the extent to which differences between laboratories may affect the results when a standardised protocol is used. As a clinical tool, movement analysis techniques are helpful for the objective and quantitative assessment of kinematics. Knowledge about the repeatability of the kinematic data is very important. The present study investigates the repeatability of back kinematics in 10 sound horses over 5 successive days and in 2 laboratories (5 horses at each location). Measurements were performed on the treadmill during the walk and the trot. The between-stride, between-day and between-horse repeatability were determined. A high degree of between-stride and between-day repeatability was observed in the spatiotemporal parameters and in the time-angle diagrams of thoracic and lumbar vertebrae, the sacrum and the hindlimb during both the walk and trot. Much more variability was found between horses, with the highest degree of dissimilarity in the lateral bending rotation of the L1 vertebra. For range of motion values, the between-day coefficient of variability was <14% and the between-horse coefficient of variability was up to 4 times higher. Small differences were found in range of motion values between the 2 laboratories. It is concluded that an analysis of back kinematics in the horse can provide highly repeatable data, warranting clinical use.

Animals↗
PubMed2001

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Neurobehavioral phenotype in carriers of the fragile X premutation.

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty-five female carriers of the pM with allele sizes ranging from 59-166 were administered a comprehensive IQ test (WAIS-III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)-90-R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow-up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL-90-R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (> or = 100 repeats) display some clinical manifestations of fraX syndrome.

Adult↗
PubMed2001

Primary non-random X inactivation associated with disruption of Xist promoter regulation.

In this report we demonstrate primary non-random X chromosome inactivation following targeted mutagenesis of a region immediately upstream of XIST promoter P(1). In heterozygous animals there is a preferential inactivation of the targeted X chromosome in 80--90% of cells. The phenotype correlates with inappropriate activation of XIST in a proportion of the mutant XY embryonic stem cells. Strand-specific analysis revealed increased sense transcription initiating upstream of XIST promoter P(1). There was, however, no discernible effect on transcription from the antisense Tsix gene. We demonstrate that the in vitro and in vivo phenotypes are specifically attributable to the presence of a PGKneo cassette at the targeted locus. These findings are discussed in the context of understanding mechanisms of XIST gene regulation in X inactivation.

Alleles↗
PubMed2001

Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer.

Immunohistochemical staining of human breast tissues, using an antibody against fibroblast growth factor receptor 3 [FGFR-3], showed differences in cellular distribution. Both malignant and non-malignant epithelial cells contained FGFR-3 immunoreactivity, but myoepithelial cells and stroma were negative. The staining pattern in malignant epithelial cells was predominantly nuclear, whereas epithelial cells in normal breast tissue showed both cytoplasmic and nuclear elements. Reverse transcription-polymerase chain reaction (RT-PCR) revealed two isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously described exon-deleted nuclear form of FGFR-3, which were present in both malignant and non-malignant epithelial cells. The higher level of nuclear staining and loss of cytoplasmic staining seen in malignant epithelial cells did not correspond to an increase in expression of the exon-deleted form of FGFR-3, nor to any detectable activating point mutations. Since receptor activation can result in its movement to a perinuclear localization, an alternative explanation for the redistribution of FGFR-3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9). No FGF9 was detected by immunohistochemistry in breast tissues. FGF1, however, is present in the majority of breast cancers and a different tissue distribution of FGF1 was found in breast tissues, showing predominantly nuclear, or a mix of nuclear and cytoplasmic FGFR-3. The difference in FGFR-3 staining patterns may implicate this ligand-receptor pair in breast cancer.

Adult↗